A protein tyrosine kinase is an enzyme which can transfer a phosphate group from ATP to a tyrosine residue located in protein substrates, the protein tyrosine kinase plays a role in normal cell growth. Many growth factor receptor proteins work via the protein tyrosine kinase and affect the signal via this process and then regulate cell growth, such as FGFR (fibroblast growth factor receptor), VEGFR (vascular endothelial growth factor receptor) and PDGFR (platelet-derived growth factor receptor). However, under certain conditions, these receptors mutate or overexpress and become abnormal, thereby causing uncontrolled cell proliferation, resulting in tumor growth, and eventually leading to a well-known disease, i.e., cancer. Growth factor receptor protein tyrosine kinase inhibitors play a role in the treatment of cancer and other diseases characterized by uncontrolled or abnormal cell growth by inhibiting the above phosphorylation process.
Uncontrolled angiogenesis is a sign of cancer. In 1971, Dr. Judah Folkman raised that tumor growth depends on angiogenesis (see Folkman, New England Journal of Medicine, 285: 1182-86 (1971)). According to Dr. Judah Folkman, the tumor can only grow to a certain size without additional blood vessels to nourish the tumor. In his simplest expression, it is pointed out that once a tumor has “survived”, each increase in the population of tumor cells must be carried out by the increase in the number of new capillaries that converge on the tumor. According to the current understanding, the tumor's “survival” refers to the anterior phase of tumor growth, where the tumor cells which have a volume of several cubes of millimeters and no more than several million cells can survive on the existing host microvasculature.
It has been shown that the tumor can be treated by inhibiting angiogenesis rather than inhibiting the proliferation of tumor cells themselves. Angiogenesis has been associated with a large number of different types of cancer, which include solid tumors and blood-borne tumors. Solid tumors associated with angiogenesis include, but are not limited to rhabdomyosarcoma, retinoblastoma, ewing sarcoma, neuroblastoma and osteosarcoma. Angiogenesis is associated with breast cancer, prostate cancer, lung cancer, and colon cancer. Angiogenesis is also associated with blood-borne tumors, such as leukemia, lymphoma, multiple myeloma, and any one of various acute or chronic myeloid neoplasms, in which the presence of uncontrolled proliferation of white blood cells is usually accompanied by anemia, weakened blood clotting, and increased lymph nodes, liver and spleen, and it is believed that angiogenesis plays a role in bone marrow abnormalities, and the abnormalities cause leukemia, lymphoma and multiple myeloma.
Angiogenesis plays a major role in the metastasis of cancer, and if it is possible to inhibit or eliminate the activity of the blood vessel, it will not grow even if the tumor is present. In the disease state, the prevention of angiogenesis can reduce the damage caused by the invasion of the new microvascular system. Controlled therapy for a vasculogenic process may result in the removal or reduction of these diseases.
Wherein, the research that FGFR (fibroblast growth factor receptor), VEGFR (vascular endothelial growth factor receptor) and PDGFR (platelet-derived growth factor receptor) inhibitors inhibit angiogenesis is more and more mature.